The long-term objective of this proposal is to contribute to our understanding of CNS function and of processes controlling recovery of function in the CNS following injury. In this proposal we focus on electrophysiological studies of some of the cellular and molecular mechanisms underlying neurite growth, neurite regneration and synaptic plasticity in the CNS. It is difficult to apply electrophysiological techniques to the study of the electrical properties of small axons and dendrites. It is also difficult to record activity from many CNS neurons at many loci simultaneously or to search for synaptic connections which are formed during reinnervation. To overcome this difficulty, we developed, during the initial stages of the project, a novel technology of spectroscopic electrophysiology to study mammalian neurons. Using this technique it has been possible to (i) monitor simultaneously electrical activity from multiple sites on the processes and growth cones of single cells in culture, (ii) to detect activity of many neurons at many locations simultaneously, (iii) to map functional synaptic connections in mouse spinal cord explants and rat brain slices. Using a computer interface and a TV monitor, the images of nerve cells light up when they are active. The spread of electrical activity can be literally visualized in slow motion or real time. Our objectives for the next three years are (1) to examine whether CA++ enter into growth cones play a role in the regulation of neurite growth and regeneration in vitro under controlled conditions; (2) to study the functional plasticity of synaptic connections in local circuits in the hippocampus; and (3) to evaluate detailed topographical maps and functional properties of reformed synaptic connections during reinnervation in the CNS. Further improvement of the new techniques are also proposed.